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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Airway and Blood Monocyte Transcriptomic Profiling Reveals an Antiviral Phenotype in Infants With Severe Respiratory
K Chappin1, S B Besteman2, M P Hennus3
1Center for Translational Immunology, University Medical Centre Utrecht, Utrecht University.
Insights
Respiratory syncytial virus (RSV) infection activates antiviral responses in both airway and blood monocytes. This study reveals RSV promotes monocyte migration, potentially contributing to severe disease in children.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in young children.
- The precise role of monocytes in RSV pathogenesis remains unclear.
- Understanding monocyte involvement is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the function of monocytes in severe RSV infections.
- To compare transcriptomic profiles of blood and airway monocytes during RSV infection.
Main Methods:
- Collected tracheobronchial aspirates and blood samples from pediatric patients with and without RSV.
- Isolated monocytes (CD14+) for RNA sequencing and transcriptomic profiling.
Main Results:
- RSV-infected monocytes exhibited heightened expression of antiviral and interferon-responsive genes.
- Shared cytokine signaling pathways were observed in both blood and airway monocytes.
- Airway monocytes displayed enhanced upregulation of genes associated with migration and inflammation.
Conclusions:
- The interferon response to RSV extends from the airways to peripheral blood monocytes.
- RSV infection triggers a transcriptional program that promotes monocyte migration.
- Further research into monocyte responses could lead to novel therapeutics for severe RSV disease.
Background:
Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children <5 years of age. Monocytes, especially in the respiratory tract, are suggested to contribute to RSV pathology, but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection.
Methods:
Tracheobronchial aspirates and blood samples were collected from control patients (n = 9) and those infected with RSV (n = 14) who were admitted to the pediatric intensive care unit. Monocytes (CD14+) were sorted and analyzed by RNA sequencing for transcriptomic profiling.
Results:
Peripheral blood and airway monocytes of patients with RSV demonstrated increased expression of antiviral and interferon-responsive genes as compared with controls. Cytokine signaling showed a shared response between blood and airway monocytes while displaying responses that were more pronounced according to the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation.
Conclusions:
We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unraveling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease.
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